Greater Weight Gain in Treatment-naive Persons Starting Dolutegravir-based Antiretroviral Therapy

Abstract

Background: Recent studies have reported weight gain in virologically suppressed persons living with human immunodeficiency virus (PLWH) switched from older antiretroviral therapy (ART) to newer integrase strand transfer inhibitor (INSTI)-based regimens. In this study, we investigated whether weight gain differs among treatment-naive PLWH starting INSTI-based regimens compared to other ART regimens.

Methods: Adult, treatment-naive PLWH in the Vanderbilt Comprehensive Care Clinic cohort initiating INSTI-, protease inhibitor (PI)-, and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART between January 2007 and June 2016 were included. We used multivariable linear mixed-effects models to generate marginal predictions of weights over time, adjusting for baseline clinical and demographic characteristics. We used restricted cubic splines to relax linearity assumptions and bootstrapping to generate 95% confidence intervals.

Results: Among 1152 ART-naive PLWH, 351 initiated INSTI-based regimens (135 dolutegravir, 153 elvitegravir, and 63 raltegravir), 86% were male, and 49% were white. At ART initiation, median age was 35 years, body mass index was 25.1 kg/m2, and CD4+ T-cell count was 318 cells/μL. Virologic suppression at 18 months was similar between different ART classes. At all examined study time points, weight gain was highest among PLWH starting dolutegravir. At 18 months, PLWH on dolutegravir gained 6.0 kg, compared to 2.6 kg for NNRTIs (P < .05), and 0.5 kg for elvitegravir (P < .05). PLWH starting dolutegravir also gained more weight at 18 months compared to raltegravir (3.4 kg) and PIs (4.1 kg), though these differences were not statistically significant.

Conclusions: Treatment-naive PLWH starting dolutegravir-based regimens gained significantly more weight at 18 months than those starting NNRTI-based and elvitegravir-based regimens.

Keywords: HIV metabolic complications; integrase strand transfer inhibitors; treatment-naive adults with HIV; weight gain.

Figure 1.

Changes in weight within 18 months of treatment initiation among persons living with human immunodeficiency virus, by antiretroviral regimen. Abbreviations: ART, antiretroviral therapy; DTG, dolutegravir; EVG, elvitegravir; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; RAL, raltegravir.

Figure 2.

Changes in weight within 18 months of treatment initiation among persons living with human immunodeficiency virus starting dolutegravir and elvitegravir (A) or dolutegravir and raltegravir (B). Abbreviations: ART, antiretroviral therapy; DTG, dolutegravir; EVG, elvitegravir; RAL, raltegravir.

Figure 3.

Changes in weight within 18 months of treatment initiation among persons living with human immunodeficiency virus starting dolutegravir and nonnucleoside reverse transcriptase inhibitors (A) or dolutegravir and protease inhibitors (B). Abbreviations: ART, antiretroviral therapy; DTG, dolutegravir; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Figure 4.

Changes in weight within 18 months of treatment initiation among persons living with human immunodeficiency virus starting elvitegravir and nonnucleoside reverse transcriptase inhibitors (A) or elvitegravir and protease inhibitors (B). Abbreviations: ART, antiretroviral therapy; EVG, elvitegravir; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor.